The broad, long-term objective of this project is to advance understanding of the functional and morphological organization of the hypothalamo- neurohypophysial system, which is responsible for the secretion of the hormones vasopressin (VP) and oxytocin (OT). The approach is multidisciplinary and involves 1) correlating release of VP from the neural lobe of the pituitary gland while monitoring electrical activity of magnocellular neurosecretory neurons of the hypothalamus; 2) morphological and immunochemical identification of electrophysiologically characterized neurons in the supraoptic nucleus (SON); and 3) ultrastructural identification of changes in the neurohypophysis resulting from electrical activity. Much of the work is carried out on a model system, the rat supraoptico-neurohypophysial explant, wherein the electrophysiological and hormone-secreting behaviors of neurons in the tuberal portion of the supraoptic nucleus (SONt) can be analyzed. In addition, some of the intracellular electrophysiological investigations will also be carried out in the principal SON, in order to increase the sample of immunochemically identified oxytocin neurons. The specific aims for the proposed research period are: 1) to continue the quantitative assessment of the relationship between the electrical activity of intact supraoptic neurons and VP release at a higher temporal resolution than previously possible; 2) to examine whether identified VP and OT neurons differ in their light and electron microscopic morphology; 4) to examine whether VP and OT neurons can be distinguished electrically by examining passive membrane properties, spike frequency-dependent changes (spike broadening and hyperpolarizing afterpotential), and in their response to the neurotransmitters, histamine and noradrenaline; and 5) to determine whether a burst of spikes induces morphological changes within the neural lobe, and the dependence of any such changes upon the increase in extracellular potassium or hormone release which are known to result from the burst. Study of the hypothalamo-neurohypophysial system provides a means of examining the relationship between electrical activity and hormone release, as well as their morphological correlates. Since it is known that many cells, even non-neuronal in nature, also exhibit electrical activity when releasing hormones, the questions answered by these studies could well be applicable to many cell types in the body. Vasopressin in particular is very important in determining proper water balance in all mammals, including man, and dysfunctions in its control lead to many pathological conditions, such as diabetes insipidus and chronic hypernatremia.